Platelets are born with a lit fuse. These clotting cells are set to implode when the fuse—its allotment of Bcl-xL—is burnt up, based on findings from Kylie Mason, Benjamin Kile, David Huang, and colleagues (Walter and Eliza Hall Institute, Melbourne, Australia).

Life is short for platelets, which survive only about ten days before they are removed from the bloodstream. Platelet numbers are thus set by a balance between their production and removal. Mason et al. found that this balance shifted in mice with mutated versions of the antiapoptotic protein Bcl-xL: the mice were severely deficient in platelet numbers.

An apoptotic-like mechanism is needed during the birth of platelets, which are shed from bone marrow megakaryocytes. “We thought this would be the problem,” says Kile, “but it's not.” The platelets were shed normally. “Then we had an exciting thought: what if [Bcl-xL] is keeping the platelets alive?” Kile and colleagues now show that Bcl-xL provides “a beautiful dose-dependent regulation of lifespan.”

Bcl-xL protected platelets from death by restraining deadly Bak, which pokes holes in mitochondrial membranes and induces caspase-mediated apoptosis. The authors propose that platelets start out with enough Bcl-xL to block Bak. But because Bcl-xL is more labile, Bak eventually wins out. The Bcl-xL mutants were even more labile than normal, resulting in those platelets' early demise.

Because platelets lack nuclei, they cannot synthesize replacement Bcl-xL. Their lifespan is thus predetermined by their megakaryocyte-donated allotment even in the absence of an external death signal.

Apoptotic inhibitors might have future use in vivo to boost platelet numbers in clotting-deficient patients. But Kile is excited about a more immediate possibility—that Bak inhibitors might extend the very short shelf life of donated platelets used in transfusions. “Even just a 50% increase would be a huge gain in the clinical setting,” he says.